The present invention generally relates to enhancing the biocompatibility of partially enclosed interior polymeric surfaces of medical devices such as tubing for catheters and the like. More particularly, the invention relates to surface activation of polymeric surfaces such as lumens of medical-grade tubing by radiofrequency plasma treatment as a step in achieving immobilization of anti-thrombogenic agents or the like onto interior polymeric surfaces. The radiofrequency plasma medium is at a substantially low pressure and includes water vapor, oxygen or combinations thereof. When this medium is subjected to radiofrequency plasma discharge conditions, the polymeric surfaces of the device being treated, including partially enclosed interior surfaces such as lumens, are activated for attachment thereto of anti-thrombogenic agents such as heparinous materials and the like.
It is well known that many medical devices must have surfaces which are of enhanced biocompatibility. It is also well-known that, generally speaking, biocompatibility properties are enhanced by attempting to secure anti-thrombogenic agents to polymeric surfaces of medical devices, particularly those which are blood-contacting surfaces to be implanted or otherwise used during medical procedures and the like. In many instances, it is particularly undesirable to have the anti-thrombogenic agent leach away in wet environments such as are encountered by medical devices that engage blood or other body fluids. At times, these surfaces in need of biocompatibility enhancement are partially enclosed interior surfaces such as lumens of catheters or other medical tubing.
Certain attempts have been made and approaches have been suggested whereby a polymeric surface is activated by treatment with a plasma which in turn reacts with heparin or the like to provide a polymeric surface having anti-thrombogenic properties. Included are patents incorporating plasma discharge treatment with a gaseous environment having a variety of gases, including inert gases and organic gases. Patents in this regard include U S. Pat. Nos. 4,613,517, No. 4,656,083 and No. 4,948,628, which mention a variety of plasma media including those generated from hydrogen, helium, ammonia, nitrogen, oxygen, neon, argon, krypton, xenon, ethylenic monomers and other hydrocarbons, halohydrocarbons, halocarbons and silanes. It will be appreciated that various ones of these plasma media are relatively expensive and can be hazardous to use within a manufacturing environment and/or to dispose of as waste. Also, certain plasma media are more suitable for treatment of specific substrates.
It is desirable to provide a surface treatment procedure which is available for use in connection with rendering anti-thrombogenic any of a number of surfaces of medical devices or the like, including partially enclosed interior surfaces. It is further desirable that any plasma deposition procedure included in this regard avoid the need to use plasma media that are expensive, potentially hazardous or otherwise difficult to handle. At the same time, any plasma media should strongly bind the anti-thrombogenic agent to the surface being treated, preferably while also accomplishing this in an especially efficient manner that is readily susceptible to use on a large scale.
While certain approaches have been suggested which are particularly designed for treating interior surfaces, these typically require specifically designed equipment and/or are not particularly useful for treating interior surfaces which are spaced a relatively long distance from the access opening to the interior surface. This situation would occur, for example, in attempting to treat a long length of small-diameter tubing such as that for an angiographic or angioplasty catheter, particularly when it is important that entire length of the tubing, including the internal surface at the mid-length of the tubing, is to be treated. In addition to the patents mentioned hereinabove, the following patents describe devices for treating surfaces such as the inside of a tubular body: U.S. Pat. Nos. 4,261,806, No. 4,692,347 and No. 4,846,101.
It has been discovered that plasma media which include a substantial concentration of water vapor or oxygen, either alone or in combination with each other, and when provided at especially low pressures, achieve especially advantageous activation of partially enclosed interior surfaces such as the lumen of an elongated, small diameter tubing, when the low-pressure plasma medium is subjected to radiofrequency plasma treatment conditions. The thus activated surface is preferably treated with a spacer component having amine moieties, particularly spacer components which have primary or secondary amine groups. An anti-thrombogenic agent or the like, typically with the assistance of a coupling agent, is covalently bound to the spacer component. The result is an evenly covered biocompatible surface that significantly avoids leaching of the anti-thrombogenic agent or the like out of the partially enclosed interior surface such as the tubing lumen.
It is accordingly a general object of the present invention to provide an improved method for treating interior polymeric surfaces and medical devices or the like having such surfaces.
Another object of this invention is to provide improved medical device components such as tubing having internal polymeric surfaces with anti-thrombogenic agents or the like immobilized thereon.
Another object of the present invention is to provide an improved anti-thrombogenic interior polymeric surface and method of making same which utilizes radiofrequency plasma discharge techniques that avoid the use of expensive or hazardous plasma media and that avoid the need for specifically designed plasma treatment equipment.
Another object of this invention is to provide an improved method for covalently binding antithrombogenic agents or the like to substantially enclosed polymeric surfaces, which agents do not leach away in wet environments, as well as to the improved substantially enclosed polymeric surfaces thus produced.
Another object of the present invention is to provide an improved process for rendering interior surfaces of medical device components, such as narrow tubing, anti-thrombogenic through a process by which the mean free path of the gaseous treatment media generally approximates the dimensions of the interior volume such as the inside diameter of medical grade tubing, whereby the reactive species are able to penetrate the inside volume of the device before they become deactivated in the gaseous phase.
These and other objects, features and advantages of this invention will be clearly understood through a consideration of the following detailed description.